Our prior studies of carbocyclic analogs of purine nucleosides and of a few pyrimidine nucleosides have uncovered significant anticancer and antiviral activity among compounds with this structure, in which the furanose ring of nucleosides is replaced by a cyclopentane ring. These analogs differ from normal nucleosides in that the pseudosugar unit is not subject to cleavage by phosphorylases and hydrolases. The observed activities by certain carbocyclic analogs, the importance of pyrimidine nucleosides among clinically active anticancer drugs, and the preeminence of nucleosides among clinically useful antiviral agents indicate a potentially important role for carbocyclic pyrimidine nucleoside analogs. For these reasons, this proposed, collaborative research program includes the synthesis of new carbocyclic pyrimidine nucleoside analogs that are either congeners of the active carbocyclic analogs or are analogs to known, active pyrimidine nucleosides. The new analogs are to be evaluated in vitro and in vivo for anticancer activity and for antiviral activity, initially in vitro, against both oncogenic and nononcogenic viruses. Analogs that show significant antiviral activity in vitro are to be further evaluated in vivo for antiviral activity. Biochemical studies are designed to determine if active analogs are enzymatically activated, to identify the locus, or loci, of action of active analogs, and to determine if antiviral analogs selectively inhibit virus-induced enzymes.